Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens.

Original publication

DOI

10.1016/j.celrep.2018.03.045

Type

Journal article

Journal

Cell rep

Publication Date

10/04/2018

Volume

23

Pages

596 - 607

Keywords

CIC, CRISPR/Cas9 screen, Capicua, GeCKO, H5N1, SLC35A1, cell-intrinsic immunity, host factors, influenza virus, sialic acid pathway, A549 Cells, CRISPR-Cas Systems, Gene Knockout Techniques, Gene Library, Genome, Human, Humans, Influenza A Virus, H5N1 Subtype, Lentivirus, Nucleotide Transport Proteins, Virus Internalization, Virus Replication